Biomedical subjects

C Cheng

Publications and source records attributed to C Cheng.

At least 127 records · Page 7Linked to original sources

PubMed1997

[Studies on biological effects of kappa-selenocarrageenan on human breast cancer cell line BCaP-37].

Proliferation, cell cycle, total amount of DNA, area of cell nucleus, as well as epidermal growth factor receptors (EGFR) and expression of oncogene C-erbB2 mRNA of Chinese breast cancer cell line (BCaP-37) after being treated with kappa-selenocarrageenan were determined by cell culture technique, image cytometry (ICM) and northern blot to explore its anti-tumor mechanism. Results revealed 3.0-120 mg/L selenocarrageenan could inhibit proliferation of BCaP-37, with a response of time and dose dependence. The areas of nuclei were significantly lower with ICM in cells treated with 15 or 60 mg/L selenocarrageenan for four days than those in controls (P < 0.01). Levels of EGFR and expression of C-erbB2 mRNA were significantly inhibited in cells treated with 60 mg/L selenocarrageenan. It suggests that selenocarrageenan can inhibit proliferation of breast cancer cells through regulation of the levels of EGFR and expression of C-erbB2 mRNA.

Antineoplastic Agents↗

PubMed1996

Initiation of glycogen synthesis in yeast. Requirement of multiple tyrosine residues for function of the self-glucosylating Glg proteins in vivo.

The self-glucosylating proteins, Glg1p and Glg2p, are required for glycogen synthesis in Saccharomyces cerevisiae (Cheng, C., Mu., J., Farkas, I., Huang, D., Goebl M. G., and Roach, P. J. (1995) Mol. Cell. Biol. 15, 6632-6640). Glg2p was shown to be associated with carbohydrate in vivo and was released from the high molecular weight glycogen fraction by treatment with alpha-amylase. In addition, some Glg2p exists as a protein of Mr approximately 43,000, whose proportion is increased in cells lacking glycogen synthase. Unlike the mammalian counterpart, glycogenin, the yeast Glg proteins appear to require multiple Tyr residues for functionality. In Glg2p, mutation of both Tyr230 and Tyr232 is necessary to suppress self-glucosylation of purified protein in vitro. The mutant protein is still capable of transferring glucose to an exogeneous acceptor, n-dodecyl beta-D-maltoside. A small COOH-terminal region, conserved between Glg1p and Glg2p, is also important for function; mutation of Tyr367 or truncation at residue 362 impairs the ability of primed Glg2p to be elongated by glycogen synthase. Complete suppression of glycogen accumulation in vivo requires mutation of all three Tyr residues. In Glg1p, two Tyr residues are implicated, Tyr232 and Tyr600, mutation of both being required to eliminate glycogen accumulation in vivo.

Amino Acid Sequence↗

PubMed1996

Thermoregulation and heart rate variability.

1. Heart rate variability is modulated by multiple control systems, including autonomic and hormonal systems. Long-term variability, i.e. the very low-frequency band of the power spectra, has been postulated to reflect thermoregulatory vasomotor control, based upon thermal entrainment experiments. However, the relationship between thermoregulatory responses (vasoconstriction and shivering) and heart rate variability has not been studied. 2. We performed two distinct protocols in a series of human subjects. In the first protocol, core temperature was reduced by intravenous infusion of cold saline, while skin temperature was unchanged. The second protocol involved skin-surface warming and cooling until shivering developed. Power spectral analysis was performed using a fast Fourier transformation, and the area in three distinct band-widths was determined. 3. Very low-frequency power (0.0039-0.04 Hz) increased significantly in response to core cooling, peripheral vasoconstriction and shivering, while both very low- and low- (0.04-0.15 Hz) frequency power increased in response to skin-surface cooling. Heart rate decreased during core cooling-induced vasoconstriction, suggesting a direct thermal response, and increased in relation to the metabolic demands associated with shivering. 4. Our results suggest that very low-frequency power is modulated by thermal stimuli which result in core hypothermia and thermoregulatory activity, while skin-surface cooling without core hypothermia does not selectively modulate this frequency band.

Adult↗

PubMed1996

Staurosporine induces a sequential program of mouse keratinocyte terminal differentiation through activation of PKC isozymes.

Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05 mM Ca2+, in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC alpha, epsilon, and/or delta were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway.

Alkaloids↗

PubMed1996

Diabetes increases sciatic nerve susceptibility to endothelin-induced ischemia.

Endothelin-1 (ET) is a potent vasoconstrictor of vasa nervorum, the vascular supply of peripheral nerve trunks, that may, through elevated circulating levels, promote microangiopathy in human diabetes patients. In previous work, we observed that sciatic nerve trunks of rats exposed to epineurial ET developed transient dose-dependent endoneurial ischemia that might be associated with reversible motor conduction block. In the present study, we explored the possibility that ET ischemia might selectively damage axons of diabetic nerve trunks. We exposed the sciatic nerves of rats with streptozotocin-induced diabetes of 6-8 weeks duration and age-matched nondiabetic controls to supramaximal vasoconstrictive concentrations of epineurial ET and studied serial regional erythrocyte flux (laser Doppler flowmeter) and sciatic tibial motor conduction for up to 14 days. In diabetic rats, but not controls, ET ischemia damaged a large proportion of sciatic axons, predicted in each instance by focal motor conduction block across the site of ET application and eventual loss of distal motor nerve excitability. Histological studies confirmed the presence of severe axonal degeneration in diabetic sciatic nerves exposed to ET. Part of the susceptibility to ET in diabetes was accounted for by more intense and prolonged vasoconstriction. Diabetic nerves are selectively susceptible to ET-mediated ischemia.

Animals↗

PubMed1995

A single amino acid substitution in zinc finger 2 of Adr1p changes its binding specificity at two positions in UAS1.

The two zinc fingers of the yeast transcription factor Adr1p recognize the 6 bp sequence TTG GAG site in which the first finger, a His-X3-His finger, recognizes the G-rich triplet (GAG) and the second zinc finger, a His-X4-His finger, recognizes the T-rich sequence (TTG). Mutations were introduced into the alpha-helical region of the second finger and the resultant mutant proteins were analyzed for DNA binding affinity and specificity in vitro and in vivo. Substituting His for Leu in the third position (+3) of the helix created a new binding specificity at two positions in the binding site. The mutant with His replacing Leu146(L146H) bound with high affinity to GGG GGG and with low affinity to TTG GGG. The single substitution at position +3 in the helix had the same effect on DNA binding specificity as substitution of the whole helix of the second finger with the helix of finger one. Changing Asp145 to Ala in the presence of His146 changed the apparent binding site of finger 2 to GT/CG. The L146H mutant zinc finger protein had the same binding specificity in vivo as in vitro. Changing the spacing between the His residues that ligand zinc in the second finger from four to three, the spacing found in the first finger of Adr1p and Zif268, did not alter the specificity or affinity of the wild-type or mutant protein.

Amino Acid Sequence↗

PubMed1995

Modulation of N-methyl-D-aspartate (NMDA) antagonist-induced darting behaviour by the peptidomimetic PAMTA.

The N-Methyl-D-Aspartate (NMDA) receptor has attracted much attention in recent years due to its involvement in both the functions and dysfunctions of CNS neurotransmission. The existence of multiple sites by which NMDA receptor channel function can be pharmacologically modified and the interaction between glutamate and other neurotransmitter systems such as dopamine, provide exciting therapeutic avenues for related CNS disorders. In the present study, a novel synthetic analogue of the endogenous brain peptide L-prolyl-L-leucyl glycinamide (PLG) has demonstrated a significant modulatory action on the NMDA receptor. On the basis of radioligand binding studies, the novel synthetic peptide 5-[1(S)-(2(S)-pyrrolidinylcarbonyl)amino-3-methylbutyl]-2- tetrazolylacetamide (PAMTA) has been suggested to act at a polyamine site on the NMDA receptor complex. Scatchard analysis of [3H]MK-801 binding revealed that in the presence of 100 microM PAMTA, a single binding site was obtained with the Kd being increased from 2.5 +/- 0.2 nM to 6.2 +/- 0.1 nM. The ability of PAMTA to inhibit the binding of [3H]MK-801 was sensitive to the presence of both spermidine (polyamine agonist) and arcaine (polyamine antagonist). Analyses of the binding profiles of various NMDA receptor antagonists support PAMTA's interaction with the polyamine site on this receptor complex. Furthermore, we have investigated the behavioural profile of the peptidomimetic PAMTA, by studying its effect on stereotypic behaviours induced by the NMDA receptor antagonist, CPP (3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid). Male Sprague-Dawley rats cannulated bilaterally into the medial prefrontal cortex were injected with PAMTA, CPP, a CPP/PAMTA combination, or a saline control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced epidermal neoplasia: potential involvement of alternate epidermal growth factor receptor ligands.

Autocrine epidermal growth factor receptor activation by transforming growth factor alpha (TGF alpha) has been implicated in growth stimulation during epithelial neoplasia. Using keratinocytes isolated from mice with genetic defects in TGF alpha expression, we tested whether TGF alpha is required for transformation by the v-rasHa oncogene. Introduction of v-rasHa into primary epidermal cultures using a retroviral vector stimulated growth of both control (TGF alpha +/+, BALB/c) and TGF alpha-deficient (TGF alpha -/-, wa-1) keratinocytes. Moreover, v-rasHa elicited characteristic changes in marker expression (keratin 1 was suppressed; keratin 8 was induced), previously shown to be associated with epidermal growth factor (EGF) receptor activation, in both TGF alpha +/+ and TGF alpha -/- keratinocytes. v-rasHa markedly increased secreted (> 10-fold) and cell-associated (2-3-fold) TGF alpha levels in keratinocytes from TGF alpha +/+ and BALB/c mice, but not TGF alpha -/- or wa-1 mice. Based on Northern blot analysis, v-rasHa induced striking up-regulation of transcripts encoding the additional EGF family members amphiregulin, heparin-binding EGF-like growth factor, and betacellulin in cultured keratinocytes from all four mouse strains. Interestingly, in addition to the normal 4.5-kilobase TGF alpha transcript, wa-1 keratinocytes expressed two additional TGF alpha transcripts, 4.7 and 5.2 kilobases long. All three transcripts were up-regulated in response to v-rasHa, as well as exogenous TGF alpha or keratinocyte growth factor treatment, and were also detected in RNA isolated from wa-1 brain and skin. In vivo, v-rasHa keratinocytes from control as well as TGF alpha-deficient mice produced squamous tumors when grafted onto nude mice, and these lesions expressed high levels of amphiregulin, heparin-binding EGF-like growth factor, and betacellulin mRNA, regardless of their TGF alpha status. These findings indicate that TGF alpha is not essential for epidermal neoplasia induced by the v-rasHa oncogene and suggest that another EGF family member(s) may contribute to autocrine growth stimulation of ras-transformed keratinocytes.

Animals↗

PubMed1995

Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract.

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract.

Adenocarcinoma↗

PubMed1995

Heat flow and distribution during induction of general anesthesia.

BACKGROUND: Core hypothermia after induction of general anesthesia results from an internal core-to-peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution. METHODS: Six minimally clothed male volunteers in an approximately 22 degrees C environment were evaluated for 2.5 control hours before induction of general anesthesia and for 3 subsequent hours. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in distal esophageal (core) temperature, leaving the core hypothermia specifically resulting from redistribution. RESULTS: Core temperature was nearly constant during the control period but decreased 1.6 +/- 0.3 degree C in the first hour of anesthesia. Redistribution contributed 81% to this initial decrease and required transfer of 46 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 1.1 +/- 0.3 degree C, with redistribution contributing only 43%. Thus, only 17 kcal was redistributed during the second and third hours of anesthesia. Redistribution therefore contributed 65% to the entire 2.8 +/- 0.5 degree C decrease in core temperature during the 3 h of anesthesia. Proximal extremity heat content decreased slightly after induction of anesthesia, but distal heat content increased markedly. The distal extremities thus contributed most to core cooling. Although the arms constituted only a fifth of extremity mass, redistribution increased arm heat content nearly as much as leg heat content. Distal extremity heat content increased approximately 40 kcal during the first hour of anesthesia and remained elevated for the duration of the study. CONCLUSIONS: The arms and legs are both important components of the peripheral thermal compartment, but distal segments contribute most. Core hypothermia during the first hour after induction resulted largely from redistribution of body heat, and redistribution remained the major cause even after 3 h of anesthesia.

Adult↗

PubMed1995

Optimal duration and temperature of prewarming.

BACKGROUND: Core hypothermia developing immediately after induction of anesthesia results largely from an internal core-to-peripheral redistribution of body heat. Although difficult to treat, redistribution can be prevented by prewarming. The benefits of prewarming may be limited by sweating, thermal discomfort, and efficacy of the warming device. Accordingly, the optimal heater temperature and minimum warming duration likely to substantially reduce redistribution hypothermia were evaluated. METHODS: Sweating, thermal comfort, and extremity heat content were evaluated in seven volunteers. They participated on two study days, each consisting of a 2-h control period followed by 2 h of forced-air warming with the heater set on "medium" (approximately 40 degrees C) or "high" (approximately 43 degrees C). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, ten skin temperatures, and "deep" foot temperature. RESULTS: Half the volunteers started sweating during the second hour of warming. None of the volunteers felt uncomfortably warm during the first hour of heating, but many subsequently did. With the heater set on "high," arm and leg heat content increased 69 kcal during the first 30 min of warming and 136 kcal during the first hour of warming, representing 38% and 75%, respectively, of the values observed after 2 h of warming. The increase was only slightly less when the heater was set to "medium." CONCLUSIONS: Neither sweating nor thermal discomfort limited heat transfer during the first hour of warming. Thirty minutes of forced-air warming increased peripheral tissue heat content by more than the amount normally redistributed during the first hour of anesthesia. The large increase in arm and leg heat content during prewarming thus explains the observed efficacy of prewarming.

Arm↗

PubMed1995

Increasing mean skin temperature linearly reduces the core-temperature thresholds for vasoconstriction and shivering in humans.

BACKGROUND: The contribution of mean skin temperature to the thresholds for sweating and active precapillary vasodilation has been evaluated in numerous human studies. In contrast, the contribution of skin temperature to the control of cold responses such as arteriovenous shunt vasoconstriction and shivering is less well established. Accordingly, the authors tested the hypothesis that mean skin and core temperatures are linearly related at the vasoconstriction and shivering thresholds in men. Because the relation between skin and core temperatures might vary by gender, the cutaneous contribution to thermoregulatory control also was determined in women. METHODS: In the first portion of the study, six men participated on 5 randomly ordered days, during which mean skin temperatures were maintained near 31, 34, 35, 36, and 37 degrees C. Core hypothermia was induced by central venous infusion of cold lactated Ringer's solution sufficient to induce peripheral vasoconstriction and shivering. The core-temperature thresholds were then plotted against skin temperature and a linear regression fit to the values. The relative skin and core contributions to the control of each response were calculated from the slopes of the regression equations. In the second portion of the study, six women participated on three randomly ordered days, during which mean skin temperatures were maintained near 31, 35, and 37 degrees C. At each designated skin temperature, core hypothermia sufficient to induce peripheral vasoconstriction and/or shivering was again induced by central venous infusion of cold lactated Ringer's solution. The cutaneous contributions to control of each response were then calculated from the skin- and core-temperature pairs at the vasoconstriction and shivering thresholds. RESULTS: There was a linear relation between mean skin and core temperatures at the response thresholds in the men: r = 0.90 +/- 0.06 for vasoconstriction and r = 0.94 +/- 0.07 for shivering. Skin temperature contributed 20 +/- 6% to vasoconstriction and 19 +/- 8% to shivering. Skin temperature in the women contributed to 18 +/- 4% to vasoconstriction and 18 +/- 7% to shivering, values not differing significantly from those in men. There was no apparent correlation between the cutaneous contributions to vasoconstriction and shivering in individual volunteers. CONCLUSIONS: These data indicate that skin and core temperatures contribute linearly to the control of vasoconstriction and shivering in men and that the cutaneous contributions average approximately 20% in both men and women. The same coefficients thus can be used to compensate for experimental skin temperature manipulations in men and women. However, the cutaneous contributions to each response vary among volunteers; furthermore, the contributions to the two responses vary within volunteers.

Adult↗

PubMed1995

Propofol linearly reduces the vasoconstriction and shivering thresholds.

BACKGROUND: Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 +/- 6% and 19 +/- 8%, respectively. (Skin temperature has long been known to contribute approximately 10% to the control of sweating). Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core-temperature thresholds at a single-designated skin temperature. METHODS: Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micrograms/ml; (3) a target concentration of 4 micrograms/ml; and (4) a target concentration of 8 micrograms/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees C), the propofol concentration-response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model. RESULTS: The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = -0.6 +/- 0.1 degrees C.micrograms-1.ml-1; r2 = 0.98 +/- 0.02) and shivering (slope = -0.7 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.95 +/- 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.46 +/- 0.39). CONCLUSIONS: Advantages of this new model include its being nearly noninvasive and requiring relatively little core-temperature manipulation. Propofol only slightly alters the sweating threshold, but markedly reduces the vasoconstriction and shivering thresholds. Reductions in the shivering and vasoconstriction thresholds are similar; that is, the vasoconstriction-to-shivering range increases only slightly during anesthesia.

Adult↗

PubMed1995

Requirement of the self-glucosylating initiator proteins Glg1p and Glg2p for glycogen accumulation in Saccharomyces cerevisiae.

Glycogen, a branched polymer of glucose, is a storage molecule whose accumulation is under rigorous nutritional control in many cells. We report the identification of two Saccharomyces cerevisiae genes, GLG1 and GLG2, whose products are implicated in the biogenesis of glycogen. These genes encode self-glucosylating proteins that in vitro can act as primers for the elongation reaction catalyzed by glycogen synthase. Over a region of 258 residues, the Glg proteins have 55% sequence identify to each other and approximately 33% identity to glycogenin, a mammalian protein postulated to have a role in the initiation of glycogen biosynthesis. Yeast cells defective in either GLG1 or GLG2 are similar to the wild type in their ability to accumulate glycogen. Disruption of both genes results in the inability of the cells to synthesize glycogen despite normal levels of glycogen synthase. These results suggest that a self-glucosylating protein is required for glycogen biosynthesis in a eukaryotic cell. The activation state of glycogen synthase in glg1 glg2 cells is suppressed, suggesting that the Glg proteins may additionally influence the phosphorylation state of glycogen synthase.

1,4-alpha-Glucan Branching Enzyme↗

PubMed1995

Characterizing oriented protein structural sites using biochemical properties.

A protein site is a region of a three-dimensional protein structure with a distinguishing functional or structural role. Certain sites recur in different protein structures (for example catalytic sites, calcium binding sites, and some types of turns), but maintain critical shared features. To facilitate the analysis of such protein sites, we have developed a computer system for analyzing the spatial distributions of biochemical properties around a site. The system takes a set of similar sites and a set of control nonsites, and finds differences between them. Specifically, it compares distributions of the properties surrounding the sites with those surrounding the nonsites, and reports statistically significant differences. In this paper, we use our method to analyze the features in the active site of the serine protease enzymes. We compare the use of radial distributions (shells) with 3-D grids (blocks) in the analysis of the active site. We demonstrate three different strategies for focusing attention on significant findings, based on properties of interest, spatial volumes of interest, and on the level of statistical significance. Finally, we show that the program automatically identifies conserved sequential, secondary structural and biophysical features of the serine protease active site, using noncatalytic histidine residues as a control environment.

Algorithms↗

PubMed1995

Use of prostate specific antigen (PSA) and transrectal ultrasound (TRUS) in the diagnosis of prostate cancer--a local experience.

Prostate specific antigen (PSA) and transrectal ultrasound (TRUS) are two new modalities added to improve our ability to diagnose prostate cancer at an early stage. We reviewed our own experience of 100 cancers among 579 men from August 1991 to October1994. The detection rate was 17.3%. Digital rectal examination (DRE) alone had a positive predictive value (PPV) of 39.9%. The PPV for PSA was 23%. The combination of PSA and DRE gave a PPV of 47.2%. TRUS had a PPV of 30.6%. Features of cancer on TRUS may be both hypoechoic or hyperechoic nodules which appeared to have almost equal proportions associated with cancer. The addition of age-specific ranges did not affect the PPV of PSA. The PPV of the combination of TRUS and DRE was 53%. With all 3 modalities combined, the PPV was 58.8%. An interesting finding from the study was the higher average PSA for benign and malignant disease in the local population and cases of acute retention of urine. There was a higher incidence of prostatitis and lower incidence of cancer in cases with retention of urine.

Adult↗

PubMed1995

Radical prostatectomy for prostate cancer--an experience of fifteen cases in Singapore.

Radical retropubic prostatectomy as a viable option for patients with localized prostate cancer hinges on the morbidity associated with the surgery. We assessed a group of 15 patients operated between February 1992 to September 1994 by a single surgeon to gauge the severity of short-term morbidity. Their mean age was 66.7 years (range, 40-76 years). While most of them had obstructive urinary symptoms, 4 were asymptomatic and were diagnosed by screening. Their median preoperative prostate specific antigen (PSA) was 25.9 ng/dl. The mean operative time was 110 minutes and the mean blood loss was 450 ml. One patient developed postoperative pulmonary embolism which delayed his discharge from the hospital despite routine prophylactic physical measures. The median length of hospital stay was 7 days. Eight patients had immediate total continence, while the remainder attained day-time and nocturnal continence within 1 to 3 months. Three patients had adjuvant orchidectomy. Most patients had high grade and margin positive (T3) disease but none were node positive. With a median follow-up of 7 months, none of the patients developed local or systemic recurrence. With the minimum surgical morbidity, short hospital stay and excellent continence achieved, the option of radical prostatectomy can be offered to suitable patients for curative treatment of localised prostate cancer.

Adult↗

PubMed1995

Bacillus Calmette-Guerin (BCG) in the treatment of superficial bladder cancer.

We evaluated the efficacy of immune and scarification Bacillus Calmette-Guerin (BCG) in the treatment of carcinoma in situ and prophylaxis against recurrence in patients with superficial transitional carcinoma of the bladder. A single-blind, randomised, comparative trial involving 43 patients with a median follow-up of 39 months was analysed. The end points were progression to muscle invasive disease or recurrence. The overall response rate was 93% after one to two courses. There was no difference between the two preparations and no statistically significant difference between the response or progression rates of the carcinoma in-situ or prophylactic groups. However, the response to BCG was found to be a significant prognostic indicator in a multivariate analysis.

Adult↗